Dr Fred Antson

01904 328255
Email: fred.antson@york.ac.uk

Protein-nucleic acid interactions

Career Summary

I graduated from the Moscow Institute of Physics and Technology (1986) and studied for PhD at the Institute of Crystallography (Moscow, USSR Academy of Sciences) in the laboratory of protein structure led by Boris Vainstein. During 1987-1989, as a member of a working group, I was involved in the USSR Academy of Sciences initiative to set up a synchrotron radiation station for protein crystallography at the Institute of Nuclear Physics (Novosibirsk, Russia). After a number of visits to European Molecular Biology Laboratory in Hamburg (1990-1992) where I worked with Keith Wilson, in 1992 I joined the laboratory of Guy Dodson at York. Since 1998 my research has been supported by the Wellcome Trust, this enabled me to set up a research group focused on studying structures and mechanisms of several protein-nucleic acid assemblies.

Fellowships:

  • 1998 - Wellcome Trust Research Career Development Fellowship
  • 2002 – Wellcome Trust Senior Research Fellowship
  • 2007 – Wellcome Trust Senior Research Fellowship, renewal for further 5 years

Research Summary

Our group's interests are in understanding the molecular events that control biological mechanisms and we are concentrating on protein - nucleic acid interactions because of their key role in many biological processes. The major aim is to study, by X-ray structural analysis combined with several biophysical/biochemical methods, the structure and function of protein-nucleic acid complexes present in molecular motors and in steady assemblies.

schematic diagram of viral molecular motor

Mechanism of viral DNA translocation

The mechanism of DNA translocation by double-stranded DNA viruses, such as herpes viruses and tailed bacteriophages, is investigated using bacteriophage SPP1 as a model system. During viral particle assembly, the DNA is driven into a preformed procapsid through a portal protein (shown as a ribbon diagram above), a circular assembly which exists as a 13-subunit particle in its isolated forms or as a 12-subunit particle within the viral capsid. We aim to analyse the mechanism by which structural events associated with ATP hydrolysis by the viral ATPase lead to conformational changes within the portal protein; and the mechanism by which these conformational changes cause the DNA to translocate into the viral capsid. Our current model of structural changes in the portal protein during DNA translocation into a preformed viral capsid is shown in the movie. The portal protein‘s tunnel loops are shown as ribbons with one loop colored in red; DNA is shown as a ball-and-stick model.

Protein-RNA interactions during transcription regulation

Here we use Bacillus subtilis system involving TRAP/anti-TRAP proteins and RNA as a model to study regulatory processes involving protein interactions with RNA sequences containing multiple repeated segments. The structure of TRAP/RNA complex (shown on Figure) explained the dependence of RNA binding on tryptophan. Recently, a protein of previously unknown function, now termed anti-TRAP, was shown to bind to TRAP and prevent it from interacting with RNA. We are now investigating the nature and antagonism of TRAP/anti-TRAP versus TRAP/RNA interactions.

ribbon diagram of TRAP with a single-stranded RNA molecule forming a belt around the protein.

Structure and function of several tRNA modifying enzymes

Transfer RNA (tRNA) is a key element in the process of translation, whereby genetic messages are decoded in order to synthesise protein molecules. Cellular RNAs are frequently modified at the base or ribose moieties during maturation, and the greatest number and widest diversity of such modifications are found in tRNA. These modifications have various functions, including roles in the fidelity of translation and structural stability of tRNAs. As tRNA modifying enzymes are, in general, unrelated to each other, structural studies of members of each enzyme family are essential in understanding the molecular details of specificity and catalytic function. Using computational target selection strategies we have identified representatives of several such families and recently we determined the structure of Bacillus anthracis ThiI, a tRNA modifying enzyme performing a modification widespread amongst prokaryotic tRNAs. On the Figure, the ThiI protein complexed with AMP is shown to scale with the tRNA molecule (right). The target of modification by ThiI (uridine 8) is in green.

Ribbon diagram of ThiI complexed with AMP

Selected publications

  • Structural framework for DNA translocation via the viral portal protein.
    A Lebedev, M H Krause, A L Isidro, A Vagin, E V Orlova, J Turner, E J Dodson, P Tavares and A A Antson AA, EMBO J, 2007, 26,1984-1994.
  • Papillomavirus E1 helicase assembly maintains an asymmetric state in the absence of DNA and nucleotide cofactors.
    C M Sanders, O V Kovalevskiy, D Sizov, A A Lebedev, M N Isupov and A A Antson, Nucleic Acids Research, 2007, 35, 6451–6457.
  • Transcription activator structure reveals redox control of a replication initiation reaction.
    C M Sanders, D Burgin, D Sizov, P P Seavers, M Ortiz-Lombardía and A A Antson, Nucleic Acids Research, 2007, 35:3504-3515.
  • Structural rearrangements between portal protein subunits are essential for viral DNA translocation.
    A Cuervo, M C Vaney, A A Antson, P Tavares and  L Oliveira, J Biological Chemistry, 2007, 282, 18907-18913.
  • Crystal structure of Bacillus cereus HlyIIR, the transcriptional regulator of gene for pore-forming toxin Hemolysin II.
    O V Kovalevskiy, A A Lebedev, A K Surin, A S Solonin and A A Antson, J Mol Biol, 2007, 365, 825-834.
  • Crystal Structure of Bacillus anthracis ThiI, a tRNA-modifying Enzyme Containing the Predicted RNA-binding THUMP Domain.
    D G Waterman, M Ortiz-Lombardia, M J Fogg, E V Koonin and A A Antson, Journal of Molecular Biology, 2006, 356, 97-110.
  • Structures of apo and holo tyrosine phenol-lyase reveal a catalytically critical closed conformation and suggest a mechanism for activation by K +  ions.
    D Milic, D Matkovic-Calogovic, T V Demidkina, V V Kulikova, N I Sinitzina and A A Antson, Biochemistry, 2006, 45, 7544-7552.
  • Crystal structure of Bacillus subtilis anti-TRAP protein, an antagonist  of TRAP/RNA interaction.
    M B Shevtsov, Y Chen, P Gollnick and A A Antson, Proc.  Natl. Acad. Sci. U. S. A., 2005, 102, 17600-17605.
  • Going for RNA repeats.
    P Gollnick and A Antson, Nature Structural & Molecular Biology, 2005, 12, 289 - 290.
  • Complexity in regulation of tryptophan biosynthesis in Bacillus subtilis.
    P Gollnick, P Babitzke, A Antson and C Yanofsky, Annual  Review of Genetics, 2005, 39, 47-68.
  • Structure of the intact transactivation domain of the human papillomavirus  E2 protein. A A Antson, J E Burns, O V Moroz, D J Scott, C M Sanders, I B  Bronstein, G G Dodson, K S Wilson and N J Maitland, Nature, 2000, 403,  805-809.
  • Structure of the trp RNA-binding attenuation protein, TRAP, bound to  RNA.
    A A Antson, E J Dodson, G Dodson, R B Greaves, X-P Chen and P  Gollnick, Nature, 1999, 401, 235-242.